title: A pilot phase II study of the efficacy and biosafety of doxorubicin chemotherapy in tumor-bearing equidae.
abstract: BACKGROUND
  The efficacy and biosafety of a previously established tolerable dosage of doxorubicin have not been established in horses.
  
  
  OBJECTIVE
  To provide preliminary evidence of the efficacy of doxorubicin in tumor-bearing horses, explore drug pharmacokinetics profile, and estimate period of risk of exposure to drug residues.
  
  
  METHODS
  Twelve horses with 37 tumors.
  
  
  METHODS
  Treatment protocol included 6 treatments at 3-week intervals. Eight horses were uniformly treated at a dosage of 70 mg/m(2) and 4 horses received 4 of 6 treatment cycles at 70 mg/m(2) . Clinical signs, tumor responses, and toxicoses were evaluated. Drug residue concentrations were quantitated in 3 horses receiving of 65, 70, and 75 mg/m(2) by high-performance liquid chromatography with ultraviolet detection (plasma, feces) and liquid chromatography and tandem mass spectrometry (urine).
  
  
  RESULTS
  Thirty tumors, including lymphomas, carcinomas, sarcoids, and melanoma, were evaluated for efficacy. The overall response rate was 47% (95% CI, 28-65%). Doxorubicin was not found to be effective against melanomas. Lymphomas and carcinomas were most responsive. Pooled serum Cmax and half-life of doxorubicin were 121.3 ng/mL and 12.9 hours, respectively. There were no detectable residues in fecal samples up to 3 weeks after treatment and in plasma and urine after 2 and 3 days, respectively.
  
  
  CONCLUSIONS
  This study provides preliminary evidence that single-agent doxorubicin at a dosage of 70 mg/m(2) has a broad spectrum of activity. The risk of exposure to drug residues in plasma and feces was low. Direct contact with urine-contaminated wastes should be avoided for 2 days after treatment.
authors.affiliation: Department of Surgery and Radiology, School of Veterinary Medicine, University of California, Davis, CA.
authors.forename: A P
authors.initials: AP
authors.lastname: Théon
authors.forename: N
authors.initials: N
authors.lastname: Pusterla
authors.forename: K G
authors.initials: KG
authors.lastname: Magdesian
authors.forename: L
authors.initials: L
authors.lastname: Wittenburg
authors.forename: T
authors.initials: T
authors.lastname: Marmulak
authors.forename: W D
authors.initials: WD
authors.lastname: Wilson
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004350:Drug Residues / Q000032:analysis; D006207:Half-Life; D006734:Horse Diseases / Q000188:drug therapy / Q000473:pathology*; D006736:Horses; D057230:Limit of Detection; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D010865:Pilot Projects; D012509:Sarcoma / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin
keywords: Chemotherapy; Doxorubicin; Equine; Oncology